CogniFlow-Drop: Integrated Modular System for Automated Generation of Droplets in Microfluidic Applications

Droplet microfluidics enables studying large cell populations in chemical isolation, at a single-cell resolution. Applications include studying cellular response to drugs, cell-to-cell interaction studies. Such applications need a reliable and repeatable droplet generation with high monodispersity. Most systems used in research rely on manual tuning of flow parameters on off-the-shelf instruments. Setups are highly customized, limiting reproduction of experimental results. We propose an integrated, modular system for automated aqueous droplet generation with high monodispersity. The system provides dynamic feedback control of droplet size and input pressure. Input pressure is generated by two piezoelectric micropumps. Droplet sizes are determined via light intensity measurement in an LED-photodiode setup. The system is capable of wireless communication and has a low enough power consumption for battery-powered operation. We report on the assembly and the underlying working principle, as well as an in-depth experimental evaluation of the performance of the proof-of-concept prototype in aqueous droplet generation. Evaluation was performed on a modular as well as on a system level. During module-level evaluations, aqueous droplets were generated in a light mineral oil + Span 80 surfactant carrier medium, using 3 different flow-focusing junction geometries. The presented prototype had a significantly faster pressure stabilization time (10 s) compared to a syringe pump-based reference setup (120 s). During system-level evaluation, deionized water droplets were generated in a carrier medium of HFE7500 + PEG-PFPE triblock surfactant. Resultant droplet sizes were benchmarked with microscopy. The system was able to repeatedly generate mono- and polydisperse droplets on demand, with CVs between 5-10% in the $\sim $ 50- $200 \mu \text{m}$ droplet diameter range.

Automated summary

Droplet microfluidics allows for the study of large cell populations in chemical isolation at a single-cell resolution. However, current systems rely on manual tuning and customization, limiting reproducibility. In this study, we propose an integrated, modular system for automated droplet generation with high monodispersity, providing dynamic feedback control and wireless communication. Experimental evaluations demonstrate the system's improved performance and reliability compared to existing methods.